Τίτλος:
Clinical relevance of nitrated beta 2-glycoprotein I in antiphospholipid syndrome: Implications for thrombosis risk
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Β2-Glycoprotein I (β2GPI) is an important anti-thrombotic protein and is the major auto-antigen in the antiphospholipid syndrome (APS). The clinical relevance of nitrosative stress in post translational modification of β2GPI was examined.The effects of nitrated (n)β2GPI on its anti-thrombotic properties and its plasma levels in primary and secondary APS were determined with appropriate clinical control groups. β2-glycoprotein I was nitrated at tyrosines 218, 275 and 309. β2-glycoprotein I binds to lipid peroxidation modified products through Domains IV and V. Nitrated β2GPI loses this binding (p < 0.05) and had diminished activity in inhibiting platelet adhesion to vWF under high shear flow (p < 0.01). Levels of nβ2GPI were increased in patients with primary APS compared to patients with either secondary APS (p < 0.05), autoimmune disease without APS (p < 0.05) or non-autoimmune patients with arterial thrombosis (p < 0.01) and healthy individuals (p < 0.05).In conclusion tyrosine nitration of plasma β2GPI is demonstrated and has important implications with regards to the pathophysiology of platelet mediated thrombosis in APS. Elevated plasma levels of nβ2GPI in primary APS may be a risk factor for thrombosis warranting further investigation. © 2021 Elsevier Ltd
Συγγραφείς:
Krilis, M.
Qi, M.
Ioannou, Y.
Zhang, J.Y.
Ahmadi, Z.
Wong, J.W.H.
Vlachoyiannopoulos, P.G.
Moutsopoulos, H.M.
Koike, T.
Sturgess, A.D.
Chong, B.H.
Krilis, S.A.
Giannakopoulos, B.
Περιοδικό:
Journal of Autoimmune Diseases
Εκδότης:
INSTAP Academic Press
Λέξεις-κλειδιά:
acetaldehyde; antithrombocytic agent; antivitamin K; beta2 glycoprotein 1; lipoprotein; malonaldehyde; malondialdehyde acetaldehyde; phospholipid antibody; protein; tyrosine; unclassified drug; von Willebrand factor; beta2 glycoprotein 1; nitric acid derivative, antiphospholipid syndrome; antithrombotic activity; artery thrombosis; Article; autoimmune disease; case control study; controlled study; human; human cell; human tissue; lipid peroxidation; major clinical study; multicenter study; nitration; nitrosative stress; obstetric antiphospholipid syndrome; plasma; protein binding; protein blood level; protein domain; protein processing; protein protein interaction; risk factor; shear flow; systemic lupus erythematosus; thrombocyte adhesion; vein thrombosis; antiphospholipid syndrome; blood; clinical trial; complication; immunology; metabolism; normal human; thrombocyte aggregation; thrombosis, Antiphospholipid Syndrome; beta 2-Glycoprotein I; Case-Control Studies; Healthy Volunteers; Humans; Lipid Peroxidation; Nitrates; Platelet Aggregation; Protein Processing, Post-Translational; Risk Factors; Thrombosis
DOI:
10.1016/j.jaut.2021.102675
